Response of Insulin, Glucagon, Lactate, and Nonesterified Fatty Acids to Glucose in Visceral Obesity with and without NIDDM: Relationship to Hypertension

Iannello, Silvia; Campione, Rosa; Belfiore, Francesco

doi:10.1006/mgme.1997.2670

Cited by 22 publications

(18 citation statements)

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“…11,22,23 Our data appear to be similar to those of Iannello et al 23 24 Moreover, a link between NEFA and glucagon was reported in obese subjects 11,23 In the present study, normal fasting blood glucose values were found in patients with central obesity (4.42 AE 0.3 mmolaL vs 4.28AE 0.3 mmolaL of healthy subjects) and no correlations between blood glucose (fasting and after OGTT) and glucagon concentrations were found. Therefore, the defect of a cell function and of modulation of glucagon secretion would seem to be independent of blood glucose variations in our patients with obesity of central type.…”

Section: Discussionsupporting

confidence: 91%

Serum glucagon concentration and hyperinsulinaemia influence renal haemodynamics and urinary protein loss in normotensive patients with central obesity

et al. 1999

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OBJECTIVES: Insulin-resistance syndrome and hyperinsulinaemia are linked with cardiovascular disease (CVD) in the obese population. In particular, cardiovascular risk is more frequent in central obesity and is associated with microalbuminuria (MA). MA and changes of glomerular permeability to proteins in obesity might be related with renal haemodynamic modi®cations (that is glomerular hyper®ltration). Since glucagon is physiologically involved in renal haemodynamic regulation, the purpose of this study was to examine whether changes of circulating glucagon levels might haemodynamically induce MA and proteinuria in patients with central obesity. SUBJECTS: Forty normotensive obese out-patients, 22 with central (CO group) and 18 with peripheral (PO group) body fat distribution and 11 healthy subjects. MEASUREMENTS:Serum insulin and glucagon concentrations (fasting and after oral glucose tolerance test (OGTT)) by radio immuno assay (RIA); glomerular ®ltration rate (GFR, isotopic); total clearances and urinary excretion rates of albumin (AER), IgG (IgGER) and a a1 microglobulin (computerized immunonephelometry). RESULTS: GFR and insulin concentrations (fasting and during OGTT) were higher in the CO than the PO group. Fasting glucagon concentrations were increased, and not physiologically suppressed during OGTT in patients with CO (fasting, P`0.05; OGTT 60 and 120 min, P`0.001 vs PO group). Moreover, glucagon concentrations were signi®cantly correlated with GFR in the CO group (fasting, r 0.49, P`0.05; 60 min after OGTT, r 0.58, P`0.01); whereas no correlations were found in the PO group. Higher AER (P`0.001), IgGER (P`0.001) and a1 microglobulin (P`0.05) urinary concentrations were found in patients with CO than in the PO group. CONCLUSIONS: The increase of serum glucagon concentrations may be associated with the enhancement of GFR in patients with central obesity. Glomerular hyper®ltration might in¯uence the development of MA and of proteinuria by means of a haemodynamic mechanism so contributing to increase the risk of renal microvascular complications and of CVD in central obesity.

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Section: Discussionsupporting

confidence: 91%

Serum glucagon concentration and hyperinsulinaemia influence renal haemodynamics and urinary protein loss in normotensive patients with central obesity

et al. 1999

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“…Generally, glucagon secretion by the pancreas is inhibited by hyperglycemia and stimulated by hypoglycemia. However, in animals and humans with the metabolic syndrome, glucagon secretion is augmented, rather than decreased, by an oral glucose load (Laube et al, 1974;Iannello et al, 1998;Velliquette et al, 2002). In the present study, we demonstrate that oral administration of glucose to rats with the metabolic syndrome increases glucagon levels, and this increase is accompanied by a significant increase in urinary excretion of both cAMP and adenosine.…”

Section: Discussionsupporting

confidence: 51%

“…Protocol 9: Effects of an Oral Glucose Load on Urinary Excretion of cAMP and Adenosine and on Plasma Levels of Glucagon in ZSF1 Rats. In animals and humans with the metabolic syndrome, oral glucose stimulates, rather than inhibits, glucagon release from the pancreas (Laube et al, 1974;Iannello et al, 1998;Velliquette et al, 2002). To test the role of endogenous glucagon on renal adenosine production, glucose was administered to ZSF1 rats with the metabolic syndrome (Tofovic and Jackson, 2003).…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, in obese hyperglycemic mice, a glucose challenge causes a paradoxical increase, rather than the expected decrease, in glucagon release (Laube et al, 1974). Although normal human subjects show a fall in glucagon levels in response to oral glucose, in human obese, type 2 diabetic subjects, an oral glucose increases plasma glucagon levels (Iannello et al, 1998). A 1 adenosine receptors in the renal cortex mediate vasoconstriction of the preglomerular microcirculation and augment sodium reabsorption in proximal tubules .…”

Section: Discussionmentioning

confidence: 99%

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The Pancreatohepatorenal cAMP-Adenosine Mechanism

Jackson

Mi²,

Zacharia³

et al. 2007

J Pharmacol Exp Ther

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Stimulation of adenylyl cyclase causes cellular efflux of cAMP, and cAMP (unlike adenosine) is stable in blood. Therefore, it is conceivable that cAMP could function as a circulating adenosine prohormone by local target-organ conversion of distally released cAMP to adenosine via the sequential actions of ectophosphodiesterase and ecto-5Ј-nucleotidase (cAMP f AMP f adenosine; called the cAMP-adenosine pathway). A possible specific representation of this general concept is the pancreatohepatorenal cAMP-adenosine mechanism. The pancreas secretes glucagon into the portal circulation, and glucagon is a stimulant of hepatic adenylyl cyclase. Therefore, we hypothesize that the pancreas, via glucagon, stimulates hepatic cAMP production, which provides circulating cAMP for conversion to adenosine in the kidney via the cAMP-adenosine pathway. In normal rats, intravenous cAMP increased urinary and renal interstitial (assessed by renal microdialysis) cAMP and adenosine. Intraportal infusions of glucagon increased plasma cAMP 10-fold, it did not affect plasma adenosine, and it increased urinary and renal interstitial cAMP and adenosine. Local renal interstitial blockade (by adding inhibitors directly to the microdialysis perfusate) of ectophosphodiesterase (using 3-isobutyl-1-methylxanthine or 1,3-dipropyl-8-p-sulfophenylxanthine) or ecto-5Ј-nucleotidase (using ␣,␤-methyleneadenosine-5Ј-diphosphate) prevented the cAMP-induced and glucagon-induced increases in renal interstitial adenosine, but not cAMP. In ZSF1 rats with the metabolic syndrome, an oral glucose load increased plasma glucagon and urinary cAMP and adenosine excretion. We conclude that circulating cAMP is a substrate for local conversion to adenosine via the cAMP-adenosine pathway. A specific manifestation of this is the pancreatohepatorenal cAMP-adenosine mechanism

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“…The proximal tubule expresses all components of the ECA signaling pathway necessary to form adenosine from the liver-generated cAMP (18). In animals and people with obesity, insulin resistance, and hyperlipidemia, oral glucose administration instead of inhibiting, stimulates pancreatic glucagon secretion (19,20). The excessive glucagon secreted from the pancreas, under these pathological conditions, increases the cAMP synthesized and secreted from the liver (17).…”

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confidence: 99%

The Extracellular cAMP-Adenosine Pathway Regulates Expression of Renal D1 Dopamine Receptors in Diabetic Rats

Kuzhikandathil

Clark

2011

Journal of Biological Chemistry

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Background: Mechanisms that down-regulate expression of renal D1 dopamine receptors in diabetes are not well understood. Results: Inhibiting ectonucleotidases and tissue-nonspecific alkaline phosphatase prevents D1 receptor down-regulation. Conclusion:The extracellular cAMP-adenosine (ECA) pathway is involved in the down-regulation of renal D1 receptors. Significance: Inhibitors of the ECA pathway provide a novel approach to reverse the down-regulation of D1 receptor expression in diabetic animals.

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Response of Insulin, Glucagon, Lactate, and Nonesterified Fatty Acids to Glucose in Visceral Obesity with and without NIDDM: Relationship to Hypertension

Cited by 22 publications

References 68 publications

Serum glucagon concentration and hyperinsulinaemia influence renal haemodynamics and urinary protein loss in normotensive patients with central obesity

Serum glucagon concentration and hyperinsulinaemia influence renal haemodynamics and urinary protein loss in normotensive patients with central obesity

The Pancreatohepatorenal cAMP-Adenosine Mechanism

The Extracellular cAMP-Adenosine Pathway Regulates Expression of Renal D1 Dopamine Receptors in Diabetic Rats

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